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Innate inflammation in type 1 diabetes.

Susanne M Cabrera1, Angela M Henschel1, Martin J Hessner1

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Type 1 diabetes (T1D) involves innate inflammation, particularly in children, influenced by genetics and environment. Targeting this inflammation shows promise for preventing and treating T1D.

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Area of Science:

  • Immunology
  • Endocrinology
  • Genetics

Background:

  • Type 1 diabetes (T1D) is an autoimmune disease causing lifelong insulin dependence.
  • Historically linked to adaptive immunity, T1D now shows increasing evidence of innate inflammation's role.
  • Genetic and environmental factors contribute to T1D susceptibility.

Purpose of the Study:

  • To review studies on age-dependent innate inflammation in T1D families and the T1D-susceptible biobreeding rat model.
  • To explore environmental factors like microbiome alterations, gut permeability, and viral exposures driving innate inflammation.
  • To analyze transcriptional signatures in T1D patients and their siblings to understand the natural history of innate inflammation.

Main Methods:

  • Review of existing studies on T1D pathogenesis.
  • Analysis of age-dependent innate inflammatory states in human families and a rat model.
  • Temporal measurement of plasma-induced transcriptional signatures in recent-onset T1D patients, siblings, and the biobreeding rat.
  • Investigation of potential environmental triggers for innate inflammation.

Main Results:

  • A heightened, age-dependent innate inflammatory state is observed in T1D families and the biobreeding rat.
  • Environmental factors may drive innate inflammation through altered microbiome, intestinal hyperpermeability, or viral exposures.
  • Individuals managing T1D risk develop an age-dependent immunoregulatory state, potentially explaining T1D's juvenile onset.
  • Therapeutic targeting of innate inflammation is effective in delaying T1D in rat models.

Conclusions:

  • Innate inflammation plays a significant role in Type 1 diabetes pathogenesis.
  • Understanding innate inflammation mechanisms offers insights into T1D progression and therapeutic targets.
  • Combinatorial approaches may improve clinical efficacy for innate inflammation-suppressing agents in T1D.